Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damages. Pain may be classified by etiology, duration and severity. Etiologically, pain may be classified as somatogenic (i.e. organic) or psychogenic (occurring without associated organic pathology sufficient to explain the severity and/or duration of the pain). Somatogenic pain may be further sub-classified as nociceptive (arising out of stimulation of somatic or visceral pain-sensitive nerve fibers) or neuropathic (resulting from dysfunction of the nervous system). With regard to duration, pain is generally categorized as either acute or chronic. Chronic persistent pain can cause significant impairment of physical and psychological health, and performance of social responsibilities, including work and family life. Chronic pain has been described as pain that has persisted for at least 5 days to as long as 6 months. Chronic pain is generally associated with conditions like surgery, cancer, severe injury etc. Opioids are generally used to control the severe chronic pain conditions. Although opioids are powerful analgesics, benefits are somewhat limited by relatively short half life. Since pain from the procedures described can last several days, these analgesics must be administered many times in order to be effective in controlling pain.
Tapentadol is opioid analgesic having both μ-opioid receptor agonist and noradrenalin (Norepinephrine) reuptake inhibition activity with minimal serotonin reuptake inhibition. This dual mode of action makes tapentadol particularly useful in the treatment of both nociceptive pain and neuropathic pain. Clinical trial evidence in acute and chronic non-cancer pain and neuropathic pain supports an opioid-sparing effect that reduces some of the typical opioid-related adverse effects. Specifically, the reduction in treatment-emergent gastrointestinal adverse effects for tapentadol compared with equianalgesic pure μ-opioid receptor agonist results in improved tolerability and adherence to therapy.
U.S. Pat. No. 6,248,737 discloses tapentadol and its hydrochloride salt. Tapentadol is available commercially as a brand name NUCYNTA® as an immediate release oral tablet, indicated for the relief of moderate to severe acute pain and PALEXIA® RETARD as prolonged release tablet, indicated for severe chronic pain.
When tapentadol is given orally, it undergoes extensive first pass metabolism, which leads to low bioavailability (32%). About 97% of the parent compound is metabolized. None of the metabolites contributes to the analgesic activity. Eventually, the desired action is only achieved with high dose of tapentadol. Immediate release oral tapentadol is administered every 4-6 hrs while sustained release tablet is administered every 12 hrs interval. Being an opioid analgesic, tapentadol is used for the treatment of severe pain such as post operative pain, cancer pain etc. In such cases nausea & vomiting is a frequently associated problem and hence poor patient compliance is seen with oral administration. Some drawbacks to the oral administration are that unit dose may be improperly modified by a patient, resulting in a dangerous overdose, or the patient may not be capable of swallowing the medication.
Tapentadol has short duration of action which compel patient to take frequent administration of tapentadol. Additionally, like other opioids, tapentadol is also known to have abuse potential. To combat this problem, U.S. Pat. No. 8,075,872 provides abuse proof controlled release formulation of tapentadol for oral administration, for twice a daily administration.
Thus, there exists a need for an alternative dosage form, which provides prolonged release of tapentadol thereby reduces the frequency of administration. Further the alternative dosage form is required to overcome the problem associated with oral administration and to reduce the chances of abuse so that the release of the analgesic can not be manipulated by the patient or other external sources.
Tapentadol has relatively less potential to tolerance as compared to other opioids which make this the drug of choice, to be formulated for prolonged delivery among the other opioids.
Inventors of present invention have developed a new dosage form for parenteral administration, which provide prolonged release of tapentadol. Since the analgesic effect of tapentadol remains for short duration (maximum 12 hours), prolongation of the action of the drugs would significantly benefit the patients by continuously maintaining a therapeutic level of pain relief. Prolonged release of tapentadol also overcomes the problem of inadequate relief of pain due to fluctuation in dosing frequency during oral therapy.